P36 BELANTAMAB MAFODOTIN IN PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PROTEASOME INHIBITOR, ONE IMMUNOMODULATORY AGENT AND ONE ANTI-CD38 MONOCLONAL ANTIBODY: A RETRO-PROSPECTIVE ITALIAN OBSERVATIONAL STUDY
Authors: M. Offidani, S. Morè, M. Cavo, D. Derudas, F. Di Raimondo, A. Cuneo, L. Baldini, R. Della Pepa, M. Musso, M. Boccadoro, P. Musto, A. Belotti, F. Fioritoni, N. Di Renzo, A. Mele, B. Gamberi, L. De Paoli, R. Zambello, S. Grammatico, M. Brociner, F. Fazio, M. T. Petrucci
Journal: HemaSphere (2023)

Recent therapeutic advances in multiple myeloma (MM) patients, like the introduction of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs), have dramatically improved patients’ outcomes. But the occurrence of resistance is an emerging challenge resulting in a poor survival with the urgent need for effective therapies, mostly in the setting of triple-refractory MM. Belantamab mafodotin (belamaf) is the first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA) to have demonstrated efficacy in monotherapy in DREAMM-2 trial and to be approved for treatment of relapsed/refractory MM (rrMM) patients with at least four previous lines of therapy (LOT). Being real-world data of belamaf use scarce, we designed a retroprospective study aiming to evaluate its efficacy and safety in RRMM patients treated in compassionate use programmes as Named Patient Program (NPP) and Expanded Access Program (EAP) in Italy, under the aegis of European Myeloma Network (EMN). The primary endpoint was the rate of patients achieving a clinical benefit (at least minimal response according to IMWG criteria). Secondary endpoints were safety, ORR (at least PR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Eligible patients must be ≥18 years of age with a MM diagnosis according to IMWG criteria. They must have received at least 4 LOTs and be triple-refractory (at least one PI, one IMID and one anti-CD38 mAb). Overall, 67 patients have been enrolled by 18 Italian centers. Their median age was 66 years (range 42-82) and they received from 4 to 10 previous lines of therapy (median 6). ECOG was <2 in 65% of patients, MM was IgG, IgA and light chain in 60%, 19% and 21% of patients, respectively. High risk cytogenetic was observed in 22.4% and ISS3 stage in 37% of cases. CBR was 37%, ORR was 31% and at least SD was achieved in 71% of patients. After a median follow up of 12 months, median PFS was 3.7 months, median OS 12.8 months with a median DoR of 13.8 months. As for safety, the most frequent adverse events were ocular: corneal toxicity and ocular symptoms were reported in 74% and 16% of patients, respectively, but only 10% had changes in BCVA. Ocular adverse events recovered in 46% of cases so far, they requested drug discontinuation in 45% and only dose reduction in 13% of cases. Thrombocytopenia was described in 87.5% of patients, 50% of them grade 3, but reversible. Then, 8 infections, 4 infusion reactions (clinically showing as fever), one pulmonary embolism and one grade 5 secondary neoplasia were reported. Belamaf was globally discontinued in 37 patients (55%), due to disease progression in 28, death in 3, toxicity in 5, other in 1 patient. Twenty-seven patients (40%) are still alive andforty (60%) patients died (82.5% for disease progression,10% for adverse events and 7.5% others). Explorative univariate Cox regression analysis suggests that PFS was negatively affected by age>65, p=0.094 and ECOG≥2, p=0.012 In conclusion, our cohort had fewer previous LOTs but similar median age than DREAMM-2 population. We found similar outcomes in terms of ORR and OS but median PFS and DOR seems to be longer. PFS seems to be not affected by disease prognostic factors,. We observed a similar safety profile, being the ocular adverse events the most frequent ones and thrombocytopenia the second one. The most important cause of discontinuation was disease progression.